tbuckley/cabot-search huggingface dataset:
Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children
Authors: Narayan Prabhu Iyer, Alexandre T. Rotta, Sandrine Essouri, Jose Roberto Fioretto, Hannah J. Craven, Elizabeth C. Whipple, Padmanabhan Ramnarayan, Samer Abu-Sultaneh, Robinder G. Khemani
Journal: JAMA Pediatrics (2023)

Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown.To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT).MEDLINE, Embase, and CINAHL Complete through May 2022.Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS.Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA).The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury.A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension.The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.
Human <i>RELA</i> dominant-negative mutations underlie type I interferonopathy with autoinflammation and autoimmunity
Authors: Kunihiko Moriya, Tomohiro Nakano, Yoshitaka Honda, Miyuki Tsumura, Masato Ogishi, Motoshi Sonoda, Masahiko Nishitani-Isa, Takashi Uchida, Mohamed Hbibi, Yoko Mizoguchi, Masataka Ishimura, Kazushi Izawa, Takaki Asano, Fumihiko Kakuta, Daiki Abukawa, Darawan Rinchai, Peng Zhang, Naotomo Kambe, Aziz Bousfiha, Takahiro Yasumi, Bertrand Boisson, Anne Puel, Jean-Laurent Casanova, Ryuta Nishikomori, Shouichi Ohga, Satoshi Okada, Yoji Sasahara, Shigeo Kure
Journal: The Journal of Experimental Medicine (2023)

Inborn errors of the NF-κB pathways underlie various clinical phenotypes in humans. Heterozygous germline loss-of-expression and loss-of-function mutations in RELA underlie RELA haploinsufficiency, which results in TNF-dependent chronic mucocutaneous ulceration and autoimmune hematological disorders. We here report six patients from five families with additional autoinflammatory and autoimmune manifestations. These patients are heterozygous for RELA mutations, all of which are in the 3' segment of the gene and create a premature stop codon. Truncated and loss-of-function RelA proteins are expressed in the patients' cells and exert a dominant-negative effect. Enhanced expression of TLR7 and MYD88 mRNA in plasmacytoid dendritic cells (pDCs) and non-pDC myeloid cells results in enhanced TLR7-driven secretion of type I/III interferons (IFNs) and interferon-stimulated gene expression in patient-derived leukocytes. Dominant-negative mutations in RELA thus underlie a novel form of type I interferonopathy with systemic autoinflammatory and autoimmune manifestations due to excessive IFN production, probably triggered by otherwise non-pathogenic TLR ligands.
P2Y12 inhibitor monotherapy 1 to 3 mo after PCI did not differ from standard DAPT for fatal or ischemic events
Authors: Eric R. Bates
Journal: Annals of Internal Medicine (2023)

Source Citation Gragnano F, Mehran R, Branca M; Single Versus Dual Antiplatelet Therapy (Sidney-2) Collaboration. P2Y12 inhibitor monotherapy or dual antiplatelet therapy after complex percutaneous coronary interventions. J Am Coll Cardiol. 2023;81:537-552. 36754514
177Lu-DOTATATE Therapy in a Case of Castrate-Resistant Prostate Cancer With Neuroendocrine Differentiation
Authors: Qiaoqiao Shu, Xianjun Li, Xi Chen, Yue Chen, Liang Cai
Journal: Clinical Nuclear Medicine (2023)

An 84-year-old man with prostate cancer with neuroendocrine differentiation underwent PET/CT for staging. 68 Ga-prostate-specific membrane antigen PET/CT did not show significant abnormal tracer accumulation, whereas 18 F-OC ( 18 F-AlF-NOTA-octreotide) PET/CT showed elevated tracer uptake at multiple sites throughout the body. Therefore, the patient opted to receive 1 cycle of 177 Lu-DOTATATE peptide receptor radionuclide therapy with a dose of 200 mCi. Encouragingly, radiographic tumor remission and improvement of clinical symptoms were observed after only 1 cycle of treatment.
Inborn errors of human B cell development, differentiation, and function
Authors: Stuart G. Tangye, Tina Nguyen, Elissa K. Deenick, Vanessa L. Bryant, Cindy S. Ma
Journal: The Journal of Experimental Medicine (2023)

B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most important function is producing antibodies (Ab) that efficiently clear invading pathogens. This is achieved by generating memory B cells that rapidly respond to subsequent Ag exposure, and plasma cells (PCs) that continually secrete Ab. These B cell subsets maintain humoral immunity and host protection against recurrent infections for extended periods of time. Thus, the generation of antigen (Ag)-specific memory cells and PCs underlies long-lived serological immunity, contributing to the success of most vaccines. Our understanding of immunity is often derived from animal models. However, analysis of individuals with monogenic defects that disrupt immune cell function are unprecedented models to link genotypes to clinical phenotypes, establish mechanisms of disease pathogenesis, and elucidate critical pathways for immune cell development and differentiation. Here, we review fundamental breakthroughs in unraveling the complexities of humoral immunity in humans that have come from the discovery of inborn errors disrupting B cell function.
Mechanobiology of Ferroptotic Cancer Cells as a Novel “Eat‐Me” Signal: Regulating Efferocytosis through Layer‐by‐Layer Coating
Authors: Louis Van der Meeren, Iuliia Efimova, Robin Demuynck, Bogdan Parakhonskiy, Dmitri V. Krysko, Andre G. Skirtach
Journal: Advanced Healthcare Materials (2023)

The importance of the clearance of dead cells is shown to have a regulatory role for normal tissue homeostasis and for the modulation of immune responses. However, how mechanobiological properties of dead cells affect efferocytosis remains largely unknown. Here, it is reported that the Young's modulus of cancer cells undergoing ferroptosis is reduced. To modulate their Young's modulus a layer-by-layer (LbL) nanocoating is developed. Scanning electron and fluorescence microscopy confirm coating efficiency of ferroptotic cells while atomic force microscopy reveals encapsulation of the dead cells increases their Young's modulus dependent on the number of applied LbL layers which increases their efferocytosis by primary macrophages. This work demonstrates the crucial role of mechanobiology of dead cells in regulating their efferocytosis by macrophages which can be exploited for the development of novel therapeutic strategies for diseases where modulation of efferocytosis can be potentially beneficial and for the design of drug delivery systems for cancer therapy.
Disparities in Delivery of Ambulatory Surgical Care for Children
Authors: Yao Tian, Lindsay D. Allen, Martha-Conley E. Ingram, Mehul V. Raval
Journal: JAMA Network Open (2023)

This cross-sectional study characterizes the delivery of ambulatory surgical care for children across freestanding ambulatory surgery centers and hospital-based outpatient centers and tests for differences in patient characteristics and features of procedures being performed.
Pneumatic Compression–Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer–Related Lymphedema
Authors: Ingi Min, Sung Joon Lim, Gi Jeong Cheon, Minseok Suh, Kwan Sik Seo
Journal: Clinical Nuclear Medicine (2023)

Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL).Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups.Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance.Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.
Development and Validation of a Sulfa Antibiotic Allergy Clinical Decision Rule
Authors: Jamie L. Waldron, Morgan Rose, Sara Vogrin, Matthew S. Krantz, Ryan Bolotte, Elizabeth J. Phillips, Jason A. Trubiano
Journal: JAMA Network Open (2023)

This cohort study describes the adaptation of a widely used penicillin allergy clinical decision tool for evaluation of trimethoprim-sulfamethoxazole allergy.
Postoperative Spinal 18F-FDG PET Pseudoprogression Mimicking Malignancy
Authors: Penghao Liu, Jing Huang, Jie Lu, Zan Chen, Wanru Duan
Journal: Clinical Nuclear Medicine (2023)

A 60-year-old woman presented with left upper limb weakness. Spinal MRI revealed C2-C3 heterogeneous mass with no hypermetabolic foci on 18 F-FDG PET. Total resection was performed, and the pathology showed gliosis. Her limb weakness worsened 3 months after surgery. Spinal MRI revealed long intramedullary mass from medulla oblongata to C5, which showed obvious hypermetabolism under 18 F-FDG PET with an SUV max of 7.11, but 18 F-FET PET indicated mild hypermetabolism with an SUV max of 2.29. Malignancy was suspected, and C2-C4 biopsy was performed. The pathology results confirmed the diagnosis of gliosis, and the postoperative spinal 18 F-FDG PET results were considered pseudoprogression.
Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Nurmaa K. Dashzeveg, Yuzhi Jia, Youbin Zhang, Lorenzo Gerratana, Priyam Patel, Asif Shajahan, Tsogbadrakh Dandar, Erika K. Ramos, Hannah F. Almubarak, Valery Adorno-Cruz, Rokana Taftaf, Emma J. Schuster, David Scholten, Michael T. Sokolowski, Carolina Reduzzi, Lamiaa El-Shennawy, Andrew D. Hoffmann, Maroua Manai, Qiang Zhang, Paolo D'Amico, Parastoo Azadi, Karen J. Colley, Leonidas C. Platanias, Ami N. Shah, William J. Gradishar, Massimo Cristofanilli, William A. Muller, Brian A. Cobb, Huiping Liu
Journal: Cancer Discovery (2023)

Abstract Most circulating tumor cells (CTC) are detected as single cells, whereas a small proportion of CTCs in multicellular clusters with stemness properties possess 20- to 100-times higher metastatic propensity than the single cells. Here we report that CTC dynamics in both singles and clusters in response to therapies predict overall survival for breast cancer. Chemotherapy-evasive CTC clusters are relatively quiescent with a specific loss of ST6GAL1-catalyzed α2,6-sialylation in glycoproteins. Dynamic hyposialylation in CTCs or deficiency of ST6GAL1 promotes cluster formation for metastatic seeding and enables cellular quiescence to evade paclitaxel treatment in breast cancer. Glycoproteomic analysis reveals newly identified protein substrates of ST6GAL1, such as adhesion or stemness markers PODXL, ICAM1, ECE1, ALCAM1, CD97, and CD44, contributing to CTC clustering (aggregation) and metastatic seeding. As a proof of concept, neutralizing antibodies against one newly identified contributor, PODXL, inhibit CTC cluster formation and lung metastasis associated with paclitaxel treatment for triple-negative breast cancer. Significance: This study discovers that dynamic loss of terminal sialylation in glycoproteins of CTC clusters contributes to the fate of cellular dormancy, advantageous evasion to chemotherapy, and enhanced metastatic seeding. It identifies PODXL as a glycoprotein substrate of ST6GAL1 and a candidate target to counter chemoevasion-associated metastasis of quiescent tumor cells. This article is featured in Selected Articles from This Issue, p. 1949
The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer
Authors: Zheqi Li, Tianqin Li, Megan E. Yates, Yang Wu, Amanda Ferber, Lyuqin Chen, Daniel D. Brown, Jason S. Carroll, Matthew J. Sikora, George C. Tseng, Steffi Oesterreich, Adrian V. Lee
Journal: Cancer Research (2023)

Abstract As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling. Significance: A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases.
Posterior Reversible Encephalopathy Syndrome in a Child With Renovascular Hypertension
Authors: Ajay Chavan, Vimal Kumar Paliwal, Vivek Singh
Journal: JAMA Neurology (2023)

A 6-year-old child presented with headache for 1 month and seizures followed by altered consciousness for 1 day. He had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character. What is your diagnosis?
Single-cell transcriptomics suggest distinct upstream drivers of IL-17A/F in hidradenitis versus psoriasis
Authors: Jaehwan Kim, Jongmi Lee, Xuan Li, Hyun Soo Lee, Katherine Kim, Vasuma Chaparala, William Murphy, Wei Zhou, Junyue Cao, Michelle A. Lowes, James G. Krueger
Journal: Journal of Allergy and Clinical Immunology (2023)

On the basis of the mounting evidence that type 17 T (T17) cells and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologic agents used previously in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS.
Association of Total Knee Replacement Removal From the Inpatient-Only List With Outpatient Surgery Utilization and Outcomes in Medicare Patients
Authors: Derek T. Schloemann, Thomas Sajda, Benjamin F. Ricciardi, Caroline P. Thirukumaran
Journal: JAMA Network Open (2023)

Little is known about the association of total knee replacement (TKR) removal from the Medicare inpatient-only (IPO) list in 2018 with outcomes in Medicare patients.To evaluate (1) patient factors associated with outpatient TKR use and (2) whether the IPO policy was associated with changes in postoperative outcomes for patients undergoing TKR.This cohort study included data from administrative claims from the New York Statewide Planning and Research Cooperative System. Included patients were Medicare fee-for-service beneficiaries undergoing TKRs or total hip replacements (THRs) in New York State from 2016 to 2019. Multivariable generalized linear mixed models were used to identify patient factors associated with outpatient TKR use, and with a difference-in-differences strategy to examine association of the IPO policy with post-TKR outcomes relative to post-THR outcomes in Medicare patients. Data analysis was performed from 2021 to 2022.IPO policy implementation in 2018.Use of outpatient or inpatient TKR; secondary outcomes included 30-day and 90-day readmissions, 30-day and 90-day postoperative emergency department visits, non-home discharge, and total cost of the surgical encounter.A total of 37 588 TKR procedures were performed on 18 819 patients from 2016 to 2019, with 1684 outpatient TKR procedures from 2018 to 2019 (mean [SD] age, 73.8 [5.9] years; 12 240 female [65.0%]; 823 Hispanic [4.4%], 982 non-Hispanic Black [5.2%], 15 714 non-Hispanic White [83.5%]). Older (eg, age 75 years vs 65 years: adjusted difference, -1.65%; 95% CI, -2.31% to -0.99%), Black (-1.44%; 95% CI, -2.81% to -0.07%), and female patients (-0.91%; 95% CI, -1.52% to -0.29%), as well as patients treated in safety-net hospitals (disproportionate share hospital payments quartile 4: -18.09%; 95% CI, -31.81% to -4.36%), were less likely to undergo outpatient TKR. After IPO policy implementation in the TKR cohort, there were lower adjusted 30-day readmissions (adjusted difference [AD], -2.11%; 95% CI, -2.73% to -1.48%; P < .001), 90-day readmissions ( -3.23%; 95% CI, -4.04% to -2.42%; P < .001), 30-day ED visits ( -2.45%; 95% CI, -3.17% to -1.72%; P < .001), 90-day ED visits (-4.01%; 95% CI, -4.91% to -3.11%; P < .001) and higher cost per encounter ($2988; 95% CI, $415 to $5561; P = .03). However, these changes did not differ from changes in the THR cohort except for increased TKR cost of $770 per encounter ($770; 95% CI, $83 to $1457; P = .03) relative to THR.In this cohort study of patients undergoing TKR and THR, we found that older, Black, and female patients and patients treated in safety-net hospitals may have had lesser access to outpatient TKRs highlighting concerns of disparities. IPO policy was not associated with changes in overall health care use or outcomes after TKR, except for an increase of $770 per TKR encounter.
Oxidative Phosphorylation Fueled by Fatty Acid Oxidation Sensitizes Leukemic Stem Cells to Cold
Authors: Emmanuel Griessinger, Diego Pereira-Martins, Marielle Nebout, Claudie Bosc, Estelle Saland, Emiline Boet, Ambrine Sahal, Johanna Chiche, Delphine Debayle, Lucile Fleuriot, Maurien Pruis, Véronique De Mas, François Vergez, Christian Récher, Gerwin Huls, Jean-Emmanuel Sarry, Jan Jacob Schuringa, Jean-François Peyron
Journal: Cancer Research (2023)

Abstract Dependency on mitochondrial oxidative phosphorylation (OxPhos) is a potential weakness for leukemic stem cells (LSC) that can be exploited for therapeutic purposes. Fatty acid oxidation (FAO) is a crucial OxPhos-fueling catabolic pathway for some acute myeloid leukemia (AML) cells, particularly chemotherapy-resistant AML cells. Here, we identified cold sensitivity at 4°C (cold killing challenge; CKC4), commonly used for sample storage, as a novel vulnerability that selectively kills AML LSCs with active FAO-supported OxPhos while sparing normal hematopoietic stem cells. Cell death of OxPhos-positive leukemic cells was induced by membrane permeabilization at 4°C; by sharp contrast, leukemic cells relying on glycolysis were resistant. Forcing glycolytic cells to activate OxPhos metabolism sensitized them to CKC4. Lipidomic and proteomic analyses showed that OxPhos shapes the composition of the plasma membrane and introduces variation of 22 lipid subfamilies between cold-sensitive and cold-resistant cells. Together, these findings indicate that steady-state energy metabolism at body temperature predetermines the sensitivity of AML LSCs to cold temperature, suggesting that cold sensitivity could be a potential OxPhos biomarker. These results could have important implications for designing experiments for AML research to avoid cell storage at 4°C. Significance: Mitochondrial metabolism fueled by FAO alters the membrane composition and introduces membrane fragility upon cold exposure in OxPhos-driven AML and in LSCs. See related commentary by Jones, p. 2441